We propose to study in detail the solution conformation and dynamics of lysozyme from hen egg white. Of particular interest is comparison of the properties of this protein in solution and in the crystalline state. We intend to extend considerably the work which we have already carried out on this system. The major investigational tool will be high resolution proton nuclear magnetic resonance. Methods for continued resolution and assignment of the spectrum will be applied and developed. The structure of the protein in solution and in the crystalline state will be compared by interpreting the effects of lanthanide ion probes; by interpreting chemical shift data, particularly the effects of ring currents; by measuring specific relaxation effects caused by individual nuclei on other nuclei; and by accurate measurement of coupling constants. The conformational changes which occur in the protein following ionisation of groups, binding of inhibitors, and chemical modification will be studied and compared with those observed in the crystal-line state. Dynamical information concerning the structure and conformational changes will be sought by interpretation of relaxation effects and hydrogen exchange rates. An area of particular interest is the mechanism of protein folding and unfolding. Lysozyme is a unique system for such studies and we anticipate that general conclusions concerning protein structure and function can be drawn from a study in depth of this one system.